In the search for new drugs, combinatorial chemistry has assumed a major role. Combinatorial chemistry involves synthesizing a large number of different molecular structures, which can then be screened for biological activity. The most promising structure(s) possessing a desired pharmacological activity can be identified and isolated for further experimentation and/or commercial applications. In principle, an astronomically high number of new molecular structures can be synthesized and screened. Combinatorial chemistry therefore requires a way to easily and inexpensively synthesize a large number of different molecular structures. Polypeptide and polypeptoid molecules are among the molecules that may be synthesized using combinatorial chemistry.
One method of synthesizing a large number of different molecular structures simultaneously involves the use of resin beads suspended in solvent. A large number of resin beads are divided into groups, and a different reaction is performed on each group. The resin beads are then combined into a single group and mixed. This process is repeated several times, after which each resin bead has been exposed to a sequence of reactions different from most of the other resin beads, such that each resin bead has bound molecules with a structure different from the molecules bound to most of the other resin beads.
At first, combinatorial chemistry was manually implemented. See A. Furka et al, Abstract No. P-168, Xth Intl. Symp. Med. Chem. in Budapest, Hungary, August 1988 and A. Furka et al, Int. J. Peptide Protein Res., Vol. 37, pp 487-493, 1991. However, manual implementation is slow and labor intensive.
R. N. Zuckermann et al., Int. J. Peptide Protein Res., Vol. 40, pp.497-506 (1992), discloses the use of automated methods of performing combinatorial chemistry based on robotic transfer of fluids. However, single robotic arm servicing a number of individual reaction vessels causes undesirable time delays and precludes simultaneous reactions. Also, repeated handling of resin beads by the robotic arm may damage or break down some of the resin beads. In addition, providing free access for the robotic arm may require exposing the reaction vessels to the surrounding environment, making it difficult to achieve a controlled environment. Without a controlled environment, reagents may be exposed to humidity, oxygen, or other environmental elements to which they may be sensitive. Lack of a controlled environment may also present significant hazards because noxious solvents, such as dimethylsulfoxide or methylene chloride, may be released into the environment.
Sugarman et al. (U.S. Pat. No. 5,503,805) discloses an apparatus wherein resin beads suspended in solvent are transferred between a "parent vessel" and one or more reaction vessel banks by valves, tubing, and argon pressure. While avoiding the need for robotic transfer of fluid, the apparatus is very complex, and requires transfer of resin bead suspensions between distant containers, which may damage the resin beads.